1) Field of the Invention
The present invention relates to a method for producing an animal suffering from a spinal cord injury such as paraplegia, etc. due to the neurotoxicity of glutamic acid or aspartic acid and also a method for evaluating a medicament for treating a spinal cord injury, which can protect nerves by attenuating the neurotoxicity of glutamic acid or aspartic acid.
2) Description of Related Art
Spinal cord injury such as paraplegia, etc. is a serious complication of thoracoabdominal aortic aneurysm operation, and particularly the prevalence of postoperative paraplegia has been reported to range from 5% to 20%, depending on the site and extent of the aortic aneurysm and the presence or absence of aortic dissection. Numerous improvements of surgical operative techniques and pharmacological spinal cord protections have been proposed for preventing occurrence of paraplegia, but no methods have been established yet for completely avoiding this dreadful complication.
That is, it has been desired to make studies on the clarification of complicated pathophysiologic mechanism and causes of the disease as to the spinal cord injury such as paraplegia, etc. and also to make studies on development, etc. of medicaments for treating the disease, particularly studies on provision of test animals suffering from spinal cord injury such as paraplegia, etc. due to a specific cause of disease and also on provision of a method for evaluating medicaments targeted at the specific cause of disease. Up to now, it has been reported that nerve degeneration and paraplegia occur in spinal cords of rabbits subjected to infrarenal aortic isolation for 15 to 20 minutes (MARTINEZ-ARIZALA, A., J, B. LONG, D. D. RIGGAMONTI, J. M. KRAIMER, et al, 1989, Deteriorating stroke model of spinal ischemia in the rabbit is associated with a marked hyperemia, Neurology 39 (Suppl 1): 371-372), but the rabbits have not been clarified yet as to the causes for paraplegia, etc., and thus are not always to serve as preferable test animals for the above-mentioned evaluation purpose.
On the other hand, it has been recently clarified that glutamic acid and aspartic acid, which are major excitatory neurotransmitters that are abundant in the central nerve system, including the spinal cord, are potentially neurotoxic to central nerve cells (neurons) and are involved in the pathophysiologic mechanism of a variety of neuronal diseases. Furthermore, it is (now) presumed that the neurotoxicity of glutamic acid and aspartic acid takes part in the spinal cord injury such as paraplegia, etc.
Regan and Choi reported that neuro-degenation occurred in vitro in spinal cord cell cultures of rats when exposed to a glutamic acid solution. However, the neurotoxicity of glutamic acid was not directly demonstrated in vivo. According to Mangano and Schwarcz, no nerve injury was observed even when a 300 mM glutamic acid solution was infused into the hippocampus for two weeks at a rate of 0.5 .mu.l/hr. That is, no animals suffering from a spinal cord injury such as paraplegia, etc. due to exogenous glutamic acid or aspartic acid have not been obtained up to now.